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Intravenous Infusion of Nucleated Peripheral Blood Cells Restores Fertility in Mice with Chemotherapy-Induced Premature Ovarian Failure

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Departments of Obstetrics and Gynecology, University of Illinois at Chicago, 820 South Wood Street, Chicago, IL 60612, USA
2
Meharry Medical College, Nashville, TN 37011, USA
3
Georgia Reagent University, Augusta, GA 30909, USA
*
Author to whom correspondence should be addressed.
Biomedicines 2018, 6(3), 93; https://doi.org/10.3390/biomedicines6030093
Received: 4 August 2018 / Revised: 29 August 2018 / Accepted: 11 September 2018 / Published: 15 September 2018
Cancer treatment with specific chemotherapeutic agents has been well documented to have an adverse impact on female fertility leading to premature ovarian failure (POF). The objective of this study is to investigate if chemotherapeutic induced POF can be reversed by the infusion of autologous nucleated peripheral blood cells (PBMC). To reach our goal, mice were treated with a single intraperitoneal injections of busulfan and cyclophosphamide to induce POF. This was followed by transfusion of PBMC. The ovarian morphology and functional parameters were monitored by radioimmunoassay, real-time PCR, immunofluorescence and immunohistochemistry analysis. Our study showed that chemotherapy (CTX) protracted estrous cycle period and repressed E2 production. In addition, CTX decreased the expressions of steroidogenesis markers, CYP-17 synthesis, StAR (steroidogenic acute regulatory protein), and Connexin-43 protein expression in the ovarian follicles. We also observed reduced numbers and sizes of the primordial and primary follicles in CTX-treated mice compared to untreated controls (p < 0.05). When both CTX and untreated control groups were stimulated with gonadotrophin, the control group produced ten times more ova than the CTX group. Finally, the treatment of premature ovarian failure induced by CTX with autologous PBMC transfusion resulted in over-expression and a statistically significant increase in several stem cell markers and restoration of fertility. Infusion with PBMC in CTX further decreased the estrous cycle length by 2.5 times (p < 0.01). We found that transfusion of autologous PBMC to mice with chemotherapy induced POF was very effective at restoring fertility. These results are similar to other studies using bone marrow derived mesenchymal stem cells. View Full-Text
Keywords: premature ovarian failure (POF); PBMC (Peripheral blood mononucleated cells); chemotherapy; cancer; ovary premature ovarian failure (POF); PBMC (Peripheral blood mononucleated cells); chemotherapy; cancer; ovary
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MDPI and ACS Style

El Andaloussi, A.; Igboeli, P.; Amer, A.; Al-Hendy, A. Intravenous Infusion of Nucleated Peripheral Blood Cells Restores Fertility in Mice with Chemotherapy-Induced Premature Ovarian Failure. Biomedicines 2018, 6, 93.

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